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目的分析多氯联苯(PCBs)与高脂饮食暴露后SD大鼠尿液代谢组变化,探讨PCBs对糖、脂肪等代谢的影响及可能的毒性机制,并寻找潜在的候选生物标志物。方法雄性SD大鼠随机分为对照组、高脂组、PCBs组、PCBs与高脂联合暴露组。于染毒6周收集尿液样本,采集尿液的1H NMR谱,采用主成分分析法(PCA)分析数据。结果 PCA得分图显示,联合暴露组与其他3组可完全区分,表明该组动物尿液代谢特征与其他3组存在较大差异。PCA载荷图显示,联合暴露组大鼠尿液中乳酸、葡萄糖、肌酸、2-羟异戊酸含量显著上升;柠檬酸、琥珀酸、牛磺酸、马尿酸、氧化三甲胺(TMAO)含量显著下降。结论 PCBs与高脂联合暴露导致大鼠尿液中三羧酸循环的中间产物含量降低或与能量代谢相关的代谢物蓄积,可能与线粒体功能受损、能量代谢障碍有关。这些效应可能会进一步导致糖类、脂肪、氨基酸等营养物质代谢紊乱。含量发生显著变化的代谢物可能成为PCBs与高脂饮食暴露的候选毒性标志物。
OBJECTIVE: To analyze the changes of urinary metabolites of PCBs exposed to PCBs and high-fat diets and to explore the effects of PCBs on the metabolism of sugars and lipids and possible toxicological mechanisms, and to find potential candidate biomarkers. Methods Male Sprague-Dawley rats were randomly divided into control group, hyperlipidemia group, PCBs group, PCBs combined with hyperlipidemia group. Urine samples were collected 6 weeks after drug exposure. 1H NMR spectra of urine samples were collected and analyzed by principal component analysis (PCA). Results PCA score chart shows that the combined exposure group and the other three groups can be completely distinguished, indicating that the group of animals, urine metabolic characteristics and the other three groups there is a big difference. The PCA load map showed that the contents of lactate, glucose, creatine and 2-hydroxyvaleric acid in the urine of the co-exposed group increased significantly. The contents of citric acid, succinic acid, taurine, hippuric acid and trimethylamine oxide (TMAO) Decreased significantly. Conclusions Exposure of PCBs to hyperlipidemia may lead to the decrease of the content of tricarboxylic acid cycle intermediates and the accumulation of metabolites related to energy metabolism in rat urine, which may be related to the impairment of mitochondrial function and energy metabolism. These effects may further lead to metabolic disorders such as carbohydrate, fat, amino acids and other nutrients. Metabolites with significant changes in their content may be candidates for toxicological signs of PCBs exposure to high-fat diets.